Syndrome of the trephined: clinical spectrum, risk factors, and impact of cranioplasty on neurologic recovery in a prospective cohort.

Syndrome of the trephined (SoT) is an underrecognized complication after decompressive craniectomy. We aimed to investigate SoT incidence, clinical spectrum, risk factors, and the impact of the cranioplasty on neurologic recovery. Patients undergoing a large craniectomy (> 80 cm2) and cranioplasty were prospectively evaluated using modified Rankin score (mRS), cognitive (attention/processing speed, executive function, language, visuospatial), motor (Motricity Index, Jamar dynamometer, postural score, gait assessment), and radiologic evaluation within four days before and after a cranioplasty. The primary outcome was SoT, diagnosed when a neurologic improvement was observed after the cranioplasty. The secondary outcome was a good neurologic outcome (mRS 0-3) 4 days and 90 days after the cranioplasty. Logistic regression models were used to evaluate the risk factors for SoT and the impact of cranioplasty timing on neurologic recovery. We enrolled 40 patients with a large craniectomy; 26 (65%) developed SoT and improved after the cranioplasty. Brain trauma, hemorrhagic lesions, and shifting of brain structures were associated with SoT. After cranioplasty, a shift towards a good outcome was observed within 4 days (p = 0.025) and persisted at 90 days (p = 0.005). Increasing delay to cranioplasty was associated with decreased odds of improvement when adjusting for age and baseline disability (odds ratio 0.96; 95% CI, 0.93-0.99, p = 0.012). In conclusion, SoT is frequent after craniectomy and interferes with neurologic recovery. High suspicion of SoT should be exercised in patients who fail to progress or have a previous trauma, hemorrhage, or shifting of brain structures. Performing the cranioplasty earlier was associated with improved and quantifiable neurologic recovery. Graphical abstract.

Association between Quantitative MR Markers of Cortical Evolving Organization and Gene Expression during Human Prenatal Brain Development.

The relationship between structural changes of the cerebral cortex revealed by Magnetic Resonance Imaging (MRI) and gene expression in the human fetal brain has not been explored. In this study, we aimed to test the hypothesis that relative regional thickness (a measure of cortical evolving organization) of fetal cortical compartments (cortical plate [CP] and subplate [SP]) is associated with expression levels of genes with known cortical phenotype. Mean regional SP/CP thickness ratios across age measured on in utero MRI of 25 healthy fetuses (20-33 gestational weeks [GWs]) were correlated with publicly available regional gene expression levels (23-24 GW fetuses). Larger SP/CP thickness ratios (more pronounced cortical evolving organization) was found in perisylvian regions. Furthermore, we found a significant association between SP/CP thickness ratio and expression levels of the FLNA gene (mutated in periventricular heterotopia, congenital heart disease, and vascular malformations). Further work is needed to identify early MRI biomarkers of gene expression that lead to abnormal cortical development.

Brain morphological analysis in PTEN hamartoma tumor syndrome.

PTEN hamartoma tumor syndrome (PHTS) is a spectrum of hereditary cancer syndromes caused by germline mutations in PTEN. PHTS is of high interest, because of its high rate of neurological comorbidities including macrocephaly, autism spectrum disorder, and intellectual dysfunction. Since detailed brain morphology and connectivity of PHTS remain unclear, we quantitatively evaluated brain magnetic resonance imaging (MRI) in PHTS. Sixteen structural T1-weighted and 9 diffusion-weighted MR images from 12 PHTS patients and neurotypical controls were used for structural and high-angular resolution diffusion MRI (HARDI) tractography analyses. Mega-corpus callosum was observed in 75%, polymicrogyria in 33%, periventricular white matter lesions in 83%, and heterotopia in 17% of the PHTS participants. While gyrification index and hemispheric cortical thickness showed no significant differences between the two groups, significantly increased global and regional brain volumes, and regionally thicker cortices in PHTS participants were observed. HARDI tractography showed increased volume and length of callosal pathways, increased volume of the arcuate fasciculi (AF), and increased length of the bilateral inferior longitudinal fasciculi (ILF), bilateral inferior fronto-occipital fasciculi (IFOF), and bilateral uncinate fasciculus. A decrease in fractional anisotropy and an increased in apparent diffusion coefficient values of the AF, left ILF, and left IFOF in PHTS.

White matter mean diffusivity correlates with myelination in tuberous sclerosis complex.

OBJECTIVE: Diffusion tensor imaging (DTI) of the white matter is a biomarker for neurological disease burden in tuberous sclerosis complex (TSC). To clarify the basis of abnormal diffusion in TSC, we correlated ex vivo high-resolution diffusion imaging with histopathology in four tissue types: cortex, tuber, perituber, and white matter. METHODS: Surgical specimens of three children with TSC were scanned in a 3T or 7T MRI with a structural image isotropic resolution of 137-300 micron, and diffusion image isotropic resolution of 270-1,000 micron. We stained for myelin (luxol fast blue, LFB), gliosis (glial fibrillary acidic protein, GFAP), and neurons (NeuN) and registered the digitized histopathology slides (0.686 micron resolution) to MRI for visual comparison. We then performed colocalization analysis in four tissue types in each specimen. Finally, we applied a linear mixed model (LMM) for pooled analysis across the three specimens. RESULTS: In white matter and perituber regions, LFB optical density measures correlated with fractional anisotropy (FA) and inversely with mean diffusivity (MD). In white matter only, GFAP correlated with MD, and inversely with FA. In tubers and in the cortex, there was little variation in mean LFB and GFAP signal intensity, and no correlation with MRI metrics. Neuronal density correlated with MD. In the analysis of the combined specimens, the most robust correlation was between white matter MD and LFB metrics. INTERPRETATION: In TSC, diffusion imaging abnormalities in microscopic tissue types correspond to specific histopathological markers. Across all specimens, white matter diffusivity correlates with myelination.

The role of neuroimaging in predicting neurodevelopmental outcomes of preterm neonates.

Magnetic resonance imaging (MRI) is a safe and high-resolution neuroimaging modality that is increasingly used in the neonatal population to assess brain injury and its consequences on brain development. It is superior to cranial ultrasound for the definition of patterns of both white and gray matter maturation and injury and therefore has the potential to provide prognostic information on the neurodevelopmental outcomes of the preterm population. Furthermore, the development of sophisticated MRI strategies, including diffusion tensor imaging, resting state functional connectivity, and magnetic resonance spectroscopy, may increase the prognostic value, helping to guide parental counseling and allocate early intervention services.